Clinical research unit (UIC), University General Hospital Consortium, Valencia, Spain.
Curr Pharm Des. 2012;18(26):3901-38. doi: 10.2174/138161212802083743.
Cigarette smoking is the most recognized risk factor for many inflammatory diseases such as cardiovascular diseases, chronic obstructive pulmonary disease and for a number of malignances such as lung cancer. Lung cancer is currently considered the leading cause of cancer-related deaths because its aggressive nature and the lack of effective therapeutic options. Recent advances in molecular biology and immunology have improved the knowledge on different mechanisms implicated in lung cell malignant transformation, progression and metastasis, thus presenting an exciting new era for lung anticancer therapies. The way by which cigarette smoke may induce lung malignancy includes a large number of different mechanisms and substances, most of them currently unknown. Thus, identified carcinogenic compounds of cigarette smoke may induce themselves a direct cytotoxicity and mutagenic action on lung epithelial cells by means of generation of somatic mutations, epigenetic events, epithelial cell to mesenchymal cell transformations, as well as by chronic cell damage. However, the fact that there is a relative high prevalence of ex-smoker who may develop lung cancer after years of smoking cessation suggest that other causes are also implicated. Thus cigarette smoke-induced chronic lung inflammatory microenvironment, oxidative stress and cell structural alterations such as the increase of cell proliferation, angiogenesis and apoptosis arrest are irreversible processes that have a high influence in lung tumor growth. In this review we focused in current knowledge on the mechanisms implicated in cigarette smoke-induced lung chronic inflammatory processes leading to lung carcinogenesis, as well as in current therapies based on novel molecular advances.
吸烟是许多炎症性疾病（如心血管疾病、慢性阻塞性肺疾病）和一些恶性肿瘤（如肺癌）的最公认的风险因素。肺癌目前被认为是癌症相关死亡的主要原因，因为其侵袭性和缺乏有效的治疗选择。分子生物学和免疫学的最新进展提高了人们对参与肺细胞恶性转化、进展和转移的不同机制的认识，从而为肺癌的抗癌治疗带来了令人兴奋的新时代。香烟烟雾可能导致肺癌的方式包括许多不同的机制和物质，其中大多数目前尚不清楚。因此，香烟烟雾中已确定的致癌化合物可能通过体细胞突变、表观遗传事件、上皮细胞向间充质细胞转化以及慢性细胞损伤的产生，直接对肺上皮细胞产生细胞毒性和致突变作用。然而，事实上，有相当一部分曾经吸烟的人在戒烟多年后可能会患上肺癌，这表明还有其他原因也在起作用。因此，香烟烟雾引起的慢性肺部炎症微环境、氧化应激和细胞结构改变，如细胞增殖、血管生成和细胞凋亡阻滞的增加，是不可逆转的过程，对肺肿瘤的生长有很大的影响。在这篇综述中，我们重点介绍了目前关于香烟烟雾引起的肺部慢性炎症过程导致肺癌发生的机制的认识，以及基于新的分子进展的当前治疗方法。
